Application of Multivariate Analysis to Optimize Function of Cultured Hepatocytes

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• 作者：Christina Chan ; Daehee Hwang ; Gregory N. Stephanopoulos ; Martin L. Yarmush ; and George Stephanopoulos
• 刊名：Biotechnology Progress
• 出版年：2003
• 出版时间：April 2003
• 年：2003
• 卷：19
• 期：2
• 页码：580 - 598
• 全文大小：951K
• 年卷期：v.19,no.2(April 2003)
• ISSN：1520-6033

文摘

Understanding the metabolic and regulatory pathways of hepatocytes is importantfor biotechnological applications involving liver cells, including the development ofbioartificial liver (BAL) devices. To characterize intermediary metabolism in thehepatocytes, metabolic flux analysis (MFA) was applied to elucidate the changes inintracellular pathway fluxes of primary rat hepatocytes exposed to human plasmaand to provide a comprehensive snapshot of the hepatic metabolic profile. In the currentstudy, the combination of preconditioning and plasma supplementation produceddistinct metabolic states. Combining the metabolic flux distribution obtained by MFAwith methodologies such as Fisher discriminant analysis (FDA) and partial leastsquares or projection to latent structures (PLS) provided insights into the underlyingstructure and causal relationship within the data. With the aid of these analyses,patterns in the cellular response of the hepatocytes that contributed to the separationof the different hepatic states were identified. Of particular interest was the recognitionof distal pathways that strongly correlated with a particular hepatic function. Thehepatic functions investigated were intracellular triglyceride accumulation and ureaproduction. This study illustrates a framework for optimizing hepatic function and apossibility of identifying potential targets for improving hepatic functions.